Predictive Assays for Drug and Radiation Resistance

Abstract

Numerous methods exist to measure drug and radiation resistance in cell culture. Each method has committed proponents, but no method has been widely accepted for clinical application. Virtually all of the methods are based on sound biologic principles and are capable, in my view, of providing useful clinical information. However, I have also observed that even experienced investigators (and grant reviewers) tend to have unrealistic expectations and an incomplete understanding of the biologic and statistical principles relating to these assays. My message to investigators and reviewers alike will be to (1) understand the principles, (2) have realistic expectations (i.e. look to use the information as a tool for a clinical improvement which may fall short of a revolutionary breakthrough), (3) realize that calibration of these assays for clinical application is a very slow process involving considerable trial and error, and (4) demand convincing validation, but do not erect insurmountable validation barriers which prevent utilization of the assays as a tool for clinical improvement. While I am not a radiobiologist, I will also attempt to address the issue of cell culture assays for radiation resistance. Other reviews relating to assays for both radiation (Peters et al., 1984; Peters et al., 1988; Elkind, 1988) and drug resistance (Weisenthal and Lippman, 1985; Weisenthal, 1981; Von Hoff and Weisenthal, 1980; Taetle and Koziol, 1985; Von Hoff, 1987; McGuire et al., 1988; Weisenthal et al., 1988; Von Hoff, 1989; Ichihashi, 1989; Von Hoff, 1988; Von Hoff, 1990; Dendy and Hill, 1983; Hofmann et al., 1984) are available elsewhere. In vivo assays, such as the subrenal capsule assay (Bogden et al., 1988) and nude mouse xenograft assays (Guichard, 1989; Leonetti et al., 1989;Mattern et al., 1988;Bamberg et al., 1988; Houghton and Houghton, 1983) are beyond the scope of this discussion.